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Lecture 42 Hypertension Therapeutics Barry
HTN RISK FACTOR FOR:
Cerebrovascular disease
Dementia
CAD
Heart failure
Atrial fibrillation
CKD
Erectile dysfunction
Peripheral arterial disease
WHO TO SCREEN:
All adults
Modifiable risk factors for HTN: o Obesity o Poor dietary habits o High Na intake o Sedentary lifestyle o High alcohol consumption
CV RISK: all pts with HTN should undergo a CV risk assessment regardless of age
SECONDARY CAUSES:
Endocrine disorders (pheochromocytoma, Cushing’s syndrome, thyroid disease)
CKD
Renovascular disease
Primary hyperaldosteronism
Obstructive sleep apnea (OSA) Rx drugs Other
NSAIDs
Corticosteroids
Oral contraceptives & sex hormones
Decongestants
Calcineurin inhibitors
Erythropoietin
MAOIs, SNRIs, SSRIs
Midodrine
Licorice root
Stimulants (cocaine)
Salt
Excessive alcohol use
MEASUREMENT:
Use standardized techniques and validated equipment
Electronic (oscillometric) upper arm devices are preferred over auscultation
Ambulatory or home BP measurement have better predictive ability than office BP measurement
Home BP measurement recommended if ambulatory BP measurement not tolerated, not readily available or due to patient preference
Out of office BP identifies white coat HTN or masked HTN
FOUR APPROACHES: 1. Office/clinic non-automated (auscultation)
Often inaccurate o Too rapid inflation of cuff o Digit preference (i.e. rounding to 0 or 5) o Aneroid devices less likely to remain calibrated
Routine auscultatory BP is 9/6 mmHg higher than standardized research BP (primarily using oscillometric devices)
2. Office/clinic automated (oscillometric)
Use standardized technique: o Patient seated in quiet room o Set device to take measures at 1 min intervals o Take initial measurement to verify device is
registering a measurement o Leave patient alone after first measurement, and
device automatically takes subsequent readings 3. Ambulatory
Consider in patients: o Office BP above target o Fluctuating office BP o Suspected hypotension
4. Home BP:
Consider for appropriate pts with HTN, particularly: o DM or CKD o Suspected non-adherence o Suspected white coat or masked HTN
DIAGNOSTICS:
EQUIVALENT BP: Assessment BP (mmHg)
Non-automated office BP 140/90
Automated office BP 135/85
Awake ambulatory BP 135/85
24-hr ambulatory BP 130/80
Home BP 135/85
WHITE COAT HTN:
Criteria BB (mmHg)
Office BP ≥140/90
Awake ambulatory BP < 135/85
24-hr ambulatory BP < 130/80
Home BP < 135/85
Risk factors:
Women/pregnancy
Older adults
Non-smokers
Recent dx of HTN with limited number of routine office BP measurements
Mild HTN
No evidence of end-organ damage
MASKED HTN: Criteria BB (mmHg)
Office BP < 140/90
Awake ambulatory BP ≥ 135/85
24-hr ambulatory BP ≥ 130/80
Risk factors: High-normal
clinic BP
Older adults
Males
Higher BMI
Smokers
Excessive alcohol consumption
DM
Peripheral arterial disease
Orthostatic hypotension
LVH
BASELINE LABS - all pts w/ HTN should undergo:
Urinalysis
Serum Na, K and creatinine
Fasting blood gluscose or hemoglobin A1c
Lipid parameters
Standard 12-lead ECG
Lecture 42 Hypertension Therapeutics Barry
GOALS OF THERAPY:
Prevention of mortality
Prevention of morbidity (end-organ damage)
Goal is not to “normalize” BP
Follow up q2 months if BP above target
HEALTH BEHAVIOR: Reduce foods with added Na 2000 mg/day
Weight loss BMI < 25 kg/m2
Alcohol restriction ≤ 2 drinks/day
Physical activity 30-60 minutes 4-7 days/wk
Dietary patterns DASH diet
Fruits/veggies/legumes
Grains/nuts/seeds
Low fat/non-fat dairy
Lean meat/poultry/fish
Smoking cessation Smoke-free environment
Waist circumference Men <102 cm and women < 88 cm
Potassium supplementation If patients not at risk of hyperkalemia, increased dietary K intake
PHARMACOTHERAPY: ACEI/ARBs:
CONTRAINDICATIONS:
Bilateral renal artery stenosis
Hypersensitivity
Pregnancy
History of angioedema (ACEI)
ADVERSE EFFECTS: CNS Lightheadness/dizziness, fatigue, headache
ENT Angioedema (ACEI)
CVS Hypotension, orthostatic hypotension
RESP Dry cough (ACEI)
GI Nausea/vomiting, dysgeusia
GU Renal insufficiency
ENDO Hyperkalemia
DERM Rash
DRUG INTERACTIONS: K-sparing diuretics Hyperkalemia
K supplements Hyperkalemia
Lithium Increased lithium levels
NSAIDs Renal dysfunction, increased BP
SMX-TMP Hyperkalemia
ACEI/ARBs: not be used in combination for HTN (due to risk of hyperkalemia and renal insufficiency)
B-BLOCKERS:
Non-selective combination β and α blockers o Examples: carvedilol and labetalol
Intrinsic sympathomimetic activity (ISA) o Partial β agonist activity o Less negative effects HR, glucose, lipids and
respiratory system o Avoid in stable angina and/or post-MI o Examples: acebutolol and pindolol
B-blockers inferior to other anti-hypertensive agents
CONTRAINDICATIONS:
SEVERE asthma (cardioselective B-blockers may be safe in mild-mod asthma)
2o or 3o heart block
Decompensated HF
Severe PAD
Pheochromocytoma (without α-blocker)
Hypersensitivity
ADVERSE EFFECTS: CNS Fatigue, dizziness, insomnia, vivid dreams, depression,
decreased libido
CVS Bradycardia, hypotension, decreased exercise tolerance, heart block
RESP Bronchospasm
GU Impotence
ENDO Masks hypoglycemia, increases blood glucose and triglycerides, lowers HDL-C
EXT Cold extremities
DRUG INTERACTIONS:
Amiodarone Bradycardia
Non-DHP CCB Bradycardia, hypotension
Digoxin Bradycardia
NSAIDs Hypertension
Insulin Inhibits hypoglycemic response
CCBs: Non-DHP DHP
Verapamil
Diltiazem
Amlodipine
Felodipine
Nifedipine
Adverse Effects CNS Lightheadedness/dizziness, fatigue, headache
CVS Hypotension, bradycardia (non-DHP), reflex tachycardia (DHP), heart block (non-DHP), decreased exercise tolerance
GI Constipation (verapamil)
DERM Rash (diltiazem), flushing (DHP)
Other Peripheral edema (DHP)
DRUG INTERACTIONS
B-blockers (non-DHP) Bradycardia, hypotension
CYP3A4 inhibitors Increased CCB level
CYP3A4 substrates Increased CYP3A4 substrate level
CYP3A4 inducers Decreased CCB level
Lecture 42 Hypertension Therapeutics Barry
PHARMACOTHERAPY CONTINUED…
DIURETICS: CONTRAINDICATIONS:
Anuria
Gout (relative)
Hyponatremia
Severe sulfa allergy
Hypersensitivity
Breastfeeding
Hypokalemia (relative)
ADVERSE EFFECTS: CNS Lightheadedness/dizziness
CVS Hypotension, orthostatic hypotension
GI Nausea, vomiting, diarrhea
GU Renal insufficiency, interstitial nephritis, impotence
ENDO Hypokalemia, hyponatremia, hypomagnesemia, hyperglycemia, hypercalcemia, hyperuricemia
DERM Alopecia, rash, Stevens-Johnson syndrome
DRUG INTERACTIONS:
Digoxin Increase digoxin toxicity (hypoK and hypoMg)
Lithium Increase lithium level
NSAIDs Renal insufficiency
Corticosteroids Increase risk of hypoK
BP TREATMENT THRESHOLDS: Population SBP ≥
(mmHg) DBP ≥ (mmHg)
DM 130 80
High risk (target organ damage or CV risk factors) 140 90
Low risk (no target organ damage or CV risk factors) 160 100
Very elderly (≥ 80 yr of age) 160 N/A
Health behavior alone can be considered in low risk patients with BP 140-159 / 90-99 mmHg
BP TARGETS: Setting Population SBP (mmHg) DBP (mmHg)
Office High risk* ≤ 120 N/A
DM < 130 < 80
Very elderly (≥ 80 yo) < 150 N/A
All others < 140 < 90
Home or ABPM
< 135 < 85
* High-risk patients aged ≥ 50 yr with SBP ≥ 130 Caution initiating pharmacotherapy in patients with CAD if DBP is < 60 mmHg
CONSIDERATIONS:
What is the patient’s age?
Does the patient have a compelling indication?
What is/are the patient’s preferences?
What is the patient’s baseline BP?
Is the patient pregnant/of child bearing age?
Other patient factors
TREATMENT ALGORITHM: HYPERTENSION (without other compelling indications)
CONSIDERATIONS:
α-blockers are not recommended as monotherapy
B-blockers are not recommended as first-line for patients ≥ 60 yo without a compelling indication
ACE inhibitors not recommended as monotherapy for black patients
Caution initiating 2 drugs in whom adverse events are more likely (i.e. elderly, postural hypotension, hypovolemia)
COMBINATION THERAPY:
To achieve optimal blood pressure targets, multiple drugs often required
Low doses of multiple drugs > higher doses of fewer drugs (effectiveness, SEs) o 80% of BP lowering efficacy achieved at half-standard dose o Combinations of standard doses have additive BP lowering effects
Reassess patients with uncontrolled blood pressure at least every two months
Combo of 2 first-line agents can be considered for initial txt of HTN if SBP > 20 or DBP > 10 mmHg above target
ARBs and ACEIs SHOULD NOT BE USED IN COMBINATION
Caution B-blocker + non-DHP CCB (risk bradycardia and/or heart block)
Caution ACEI or ARB + K-sparing diuretic (risk renal impairment/hyperkalemia)
Lecture 42 Hypertension Therapeutics Barry
RESISTANT HTN:
CONSIDER:
Non-adherence
White coat hypertension
Drugs that ↑ BP
Suboptimal treatment
Associated conditions (ex// obesity, chronic pain, tobacco use, excessive alcohol, salt intake)
Secondary causes
APPROACH:
If not used as first-line or second-line therapy, triple drug therapy should include a diuretic when not contraindicated
o USUAL REGIMEN: ACEI/ARB + CCB + diuretic
Two-drug combinations of beta-blockers, ACEI and ARBs not proven to have clinically important antihypertensive effect
Monitor creatinine and potassium when combining K sparing diuretics, ACEI, ARBs and/or direct renin inhibitors
Consider referral to hypertension if BP still not controlled after treatment with three antihypertensive medications
TREATMENT ALGORITHM: ISOLATED SYSTOLIC HTN (without other compelling indications)
TREATMENT ALGORITHM: COMPELLING INDICATIONS (SUMMARY) – treatment algorithms on next page
IHD ACEI or ARB for most patients B-blocker or CCB for stable angina Preferred combination is ACEI and DHP CCB
Recent MI B-blocker and ACEI or ARB
LV systolic dysfunction B-blocker and ACEI or ARB ± aldosterone antagonist
LVH Do not use vasodilators (hydralazine, minoxidil)
Non-diabetic CKD ACEI or ARB first-line therapy
DM ACEI or ARB, then CCB or thiazide/like diuretics
ADHERNECE:
Emphasize benefit
Assess adherence at each visit
Incorporate taking medication as part of routine daily activity
Simplify regimen: o Long-acting once-daily medications o Combination tablets
Adherence aids
Storytelling
OTHER PRODUCTS IN CV PREVENTION: “random topic”
ASA: decreases ischemic stroke in women and MI in men (high NTTs) but increased risk of major bleeding
B-vitamins: increases B-homocysteine levels but does not actually decrease CV events
Vitamin D: NSS
Vitamin E: increases hemorrhagic stroke
Multivitamins: NSS = don’t recommend any of these products in prevention of CVD
Lecture 42 Hypertension Therapeutics Barry
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